Interactions of endocannabinoid virodhamine and related analogs with human monoamine oxidase-A and -B

Pandey, Pankaj; Chaurasiya, Narayan D.; Tekwani, Babu L.; Doerksen, Robert J.

doi:10.1016/j.bcp.2018.06.024

Cited by 14 publications

(9 citation statements)

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“…Exact structure: endogenous peroxisome proliferator-activated receptor alpha (PPAR-α) agonist (Gaetani et al 2003), antitussive activity (Wortley et al 2017), anti-inflammatory activity (Toguri et al 2018), used to treat post-traumatic stress disorder by fatty acid amide hydrolase (FAAH) inhibition (Danandeh et al 2018), useful in the treatment of neurological disorders (Pandey et al 2018), anti-nausea effect (Rock et al 2017), analgesic activity (Zubrzycki et al 2017), anticancer activity against colon cancer cells (Pagano et al 2017)…”

Section: Resultsmentioning

confidence: 99%

Biologically active metabolite(s) from haemolymph of red-headed centipede Scolopendra subspinipes possess broad spectrum antibacterial activity

et al. 2019

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The discovery of novel antimicrobials from animal species under pollution is an area untapped. Chinese red-headed centipede is one of the hardiest arthropod species commonly known for its therapeutic value in traditional Chinese medicine. Here we determined the antibacterial activity of haemolymph and tissue extracts of red-headed centipede, Scolopendra subspinipes against a panel of Gram-positive and Gram-negative bacteria. Lysates exhibited potent antibacterial activities against a broad range of bacteria tested. Chemical characterization of biologically active molecules was determined via liquid chromatography mass spectrometric analysis. From crude haemolymph extract, 12 compounds were identified including: (1) l -Homotyrosine, (2) 8-Acetoxy-4-acoren-3-one, (3) N -Undecylbenzenesulfonic acid, (4) 2-Dodecylbenzenesulfonic acid, (5) 3 H -1,2-Dithiole-3-thione, (6) Acetylenedicarboxylate, (7) Albuterol, (8) Tetradecylamine, (9) Curcumenol, (10) 3-Butylidene-7-hydroxyphthalide, (11) Oleoyl Ethanolamide and (12) Docosanedioic acid. Antimicrobial activities of the identified compounds were reported against Gram-positive and Gram-negative bacteria, fungi, viruses and parasites, that possibly explain centipede’s survival in harsh and polluted environments. Further research in characterization, molecular mechanism of action and in vivo testing of active molecules is needed for the development of novel antibacterials.

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Section: Resultsmentioning

confidence: 99%

Biologically active metabolite(s) from haemolymph of red-headed centipede Scolopendra subspinipes possess broad spectrum antibacterial activity

et al. 2019

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“…The in vitro enzyme-inhibition assay was designed to measure the effect of primaquine and NPC1161 enantiomers on catalytic activity of r hMAO-A and -B. The kynuramine oxidative deamination assay was performed in white flat-bottom 96-well plates as previously described, with minor modifications [ 63 , 70 ]. A fixed concentration of kynuramine substrate and varying concentrations of the test compounds were used to determine the IC 50 values.…”

Section: Methodsmentioning

confidence: 99%

“…The control set without inhibitor was also run simultaneously. The results were analyzed in SigmaPlot version 10 using standard double reciprocal Lineweaver–Burk plots for computing Km and Vmax values, which were further analyzed to determine the Ki values [ 63 ].…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

et al. 2021

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8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and -B. NPC1161B, the (R)-(−) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and -B. Racemic PQ and (R)-(−)-PQ both showed marginally greater (1.2- and 1.6-fold, respectively) inhibition of MAO-A as compared to MAO-B. However, (S)-(+)-PQ showed a reverse selectivity with greater inhibition of MAO-B than MAO-A. Racemic NPC1161 was a strong inhibitor of MAOs with 3.7-fold selectivity against MAO-B compared to MAO-A. The (S)-(+) enantiomer (NPC1161A) was a better inhibitor of MAO-A and -B compared to the (R)-(−) enantiomer (NPC1161B), with more than 10-fold selectivity for inhibition of MAO-B over MAO-A. The enantioselective interaction of NPC1161 and strong binding of NPC1161A with MAO-B was further confirmed by enzyme-inhibitor binding and computational docking analyses. Differential interactions of PQ and NPC1161 enantiomers with human MAOs may contribute to the enantioselective pharmacodynamics and toxicity of anti-infective 8-AQs therapeutics.

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“…All of the samples were dialyzed against potassium phosphate buffer (25 mM; pH 7.4) at 4 °C for 14–18 h (three buffer changes). Control enzyme (without inhibitor) was also run through the same procedure and the activity of the enzyme was determined before and after the dialysis [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Selective Inhibition of Human Monoamine Oxidase B by Acacetin 7-Methyl Ether Isolated from Turnera diffusa (Damiana)

et al. 2019

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The investigation of the constituents that were isolated from Turnera diffusa (damiana) for their inhibitory activities against recombinant human monoamine oxidases (MAO-A and MAO-B) in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B (IC50 = 198 nM). Acacetin 7-methyl ether (also known as 5-hydroxy-4′, 7-dimethoxyflavone) is a naturally occurring flavone that is present in many plants and vegetables. Acacetin 7-methyl ether was four-fold less potent as an inhibitor of MAO-B when compared to acacetin (IC50 = 50 nM). However, acacetin 7-methyl ether was >500-fold selective against MAO-B over MAO-A as compared to only two-fold selectivity shown by acacetin. Even though the IC50 for inhibition of MAO-B by acacetin 7-methyl ether was ~four-fold higher than that of the standard drug deprenyl (i.e., SelegilineTM or ZelaparTM, a selective MAO-B inhibitor), acacetin 7-methyl ether’s selectivity for MAO-B over MAO-A inhibition was greater than that of deprenyl (>500- vs. 450-fold). The binding of acacetin 7-methyl ether to MAO-B was reversible and time-independent, as revealed by enzyme-inhibitor complex equilibrium dialysis assays. The investigation on the enzyme inhibition-kinetics analysis with varying concentrations of acacetin 7-methyl ether and the substrate (kynuramine) suggested a competitive mechanism of inhibition of MAO-B by acacetin 7-methyl ether with Ki value of 45 nM. The docking scores and binding-free energies of acacetin 7-methyl ether to the X-ray crystal structures of MAO-A and MAO-B confirmed the selectivity of binding of this molecule to MAO-B over MAO-A. In addition, molecular dynamics results also revealed that acacetin 7-methyl ether formed a stable and strong complex with MAO-B. The selective inhibition of MAO-B suggests further investigations on acacetin 7-methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson’s disease.

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Interactions of endocannabinoid virodhamine and related analogs with human monoamine oxidase-A and -B

Cited by 14 publications

References 50 publications

Biologically active metabolite(s) from haemolymph of red-headed centipede Scolopendra subspinipes possess broad spectrum antibacterial activity

Biologically active metabolite(s) from haemolymph of red-headed centipede Scolopendra subspinipes possess broad spectrum antibacterial activity

Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

Selective Inhibition of Human Monoamine Oxidase B by Acacetin 7-Methyl Ether Isolated from Turnera diffusa (Damiana)

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